The research and development of antifungal drugs is one of the important areas of antibiotic drugs, and is also one of the areas which have always been drawing the attention of pharmaceutical researchers. With the development of the times, especially with the development of organ transplantation, and the fast propagation of AIDS, the fungal infection is also significantly increased, and particularly, the incidence of deep fungal infection is also increased remarkably, showing a tendency of continuing increasing. Therefore, it has clinical significance to control deep fungal infection effectively. Drugs for the treatment of fungal infection include polyene antibiotics produced by microorganism, for example, amphotericin B, mycostatin, etc., and synthetic drugs including bifonazole, butenafine, ketoconazole, miconazole, sertaconazole, fluconazole, etc. However, in the treatment of deep fungal infection diseases, the most effective product is still amphotericin B which almost has antifungal activity for all fungal, and the minimum inhibitory concentration (MIC) for most of the fungal is 0.02-1 μg/ml. However, amphotericin B has high toxicity, and its therapeutic dose and toxic dose are very close, which brings unsafety to the deep fungal infection patients.
In the nineties, amphotericin B liposome was first developed in Ireland, which can increase its plasma concentration and prolong its half-life to increase the administration safety; however, its preparation conditions are very strict, the emulsion particles must be extremely fine and the requirements for the equipment are very high. The research report from overseas regarding amphotericin B derivatives also includes the preparation of its salts, amides, esters, etc.
The ester derivatives, including its methyl ester, ethyl ester and acryl ester, have been reported, however, there is no report regarding its diester derivatives. Its methyl ester derivative was studied by Rutgers University, New Jersey, US, whose purpose was aiming at HIV infection. It was found that the toxicity was lowered, and it may become anti-HIV drug. However, till now, there is no further report. The amphotericin methyl ester reported by Rutgers University has to be hydrolyzed under alkaline condition by Chemical methods, and it cannot be hydrolyzed by esterase in vivo.
It is necessary to provide a new polyene ester derivative suitable for antibiotic, which can be hydrolyzed by esterase in vivo, with mild conditions, not easy to be destroyed, therefore to achieve the purpose of good effect and low toxicity.